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COMPARITIVE EVALUATION OF CLINICALLY SIGNIFICANT MACULAR EDEMA

WITH OCT & SLIT LAMP BIOMICROSCOPY.

Dr.Anu Anna Paul

This dissertation is submitted to USAIM in partial fulfillment for the

M.Ch. (Ophthal) Certification Programme December 2009

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ABSTRACT COMPARITIVE EVALUATION OF CLINICALLY SIGNIFICANT MACULAR EDEMA WITH OCT & SLIT LAMP BIOMICROSCOPY.

Aim: To study and compare OCT and biomicroscopy in evaluation of CSME Methods: After angiographic evaluation to rule out macular ischemia, 100 eyes of CSME were analyzed Results: Though spongy edema was a universal feature, OCT analysis revealed five subgroups of patients. Group 1: spongy macular thickening (100%); Group 2: Thickening with ERM (2%); Group 3: Thickening with VMT (10%); Group 4: Thickening with CME (38%); Group 5: Thickening with SRF (8%). Conclusion: OCT helps in better anatomical characterization of CSME and therefore more relevant while planning management strategies.

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SCOPE OF STUDY

Diabetic macular edema is the commonest cause of visual loss in

patients with non proliferative diabetic retinopathy and a common

cause of visual loss in PDR. According to ETDRS, early detection and

laser treatment of CSME decreases the risk of moderate visual loss by

50%. Though laser has been the standard of care till recently, many

new treatment modalities are now available in the management of

CSME. Even in the ETDRS, many patients treated with laser did not

improve and actually had a visual drop, especially those patients with

diffuse CSME. Why laser should be effective in certain subgroup and

why not in other subgroup could not be explained at that time.

Traditional methods of evaluating macular thickening including

slit lamp biomicroscopy and fundus photography are relatively

insensitive to small changes in retinal thickness and also unable to

detect specific anatomic details especially at vitreomacular interface.

Thus new techniques for quantitatively and qualitatively measuring

retinal thickness have been explored. Recent imaging techniques can

provide tomographic or cross sectional images of macula and can yield

powerful diagnostic information, which is complimentary to FFA and

fundus photo.

Optical Coherence Tomography (OCT) is a new medical diagnostic

imaging technology which can perform micrometer resolution cross-

sectional or tomographic imaging of macula. The operation of OCT is

analogous to ultrasound B-mode imaging except that light is used

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rather than acoustic waves. OCT is established in the diagnosis of

various macular disorders including CSME, macular hole, CNVM etc.1

The aim of the study was to study and classify the OCT

characteristics of clinically significant macular edema, to correlate with

vision and to compare biomicroscopy with OCT.

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MATERIALS & METHODS This was a prospective study done between April2006 and

June2006 in patients who attended the retina clinic of Chaithanya eye

Hospital, Trivandrum. 100 eyes (70 patients) of CSME were evaluated.

The study group included both Insulin dependent and non insulin

dependent PDR and NPDR patients between the age of 40 & 80 yrs. The

study population had varied glycemic levels and HbA1c evaluation was

not done. None of the patients in our study had undergone previous

focal laser or pan-retinal photocoagulation. Such patients were excluded

as these could interfere with anatomic changes at the macula and may

not be singularly due to disease manifestation. Few of the patients had

associated other systemic diseases like hypertension, nephropathy &

hypercholestremia and were on medications. The duration of diabetes

was 7yrs to 33yrs.

All patients underwent visual acuity estimation by Snellens Visual

Acuity Chart, dilated Slit lamp- 90D examination, Fundus Fluroscein

Angiography and Optical Coherence Tomography-4 by the same

examiner. We considered macular edema to be clinically significant as

defined by the Early Treatment Diabetic Retinopathy Study (ETDRS)

protocol – that is, if there was retinal thickening or hard exudates

associated with adjacent retinal thickening observed within 500 +/_50

microns of the centre of foveal avascular zone or a zone or zones of

retinal thickening 1 disc area or larger, any part of which was within 1

disc diameter of the center of the macula.

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We classified patients into 4 groups based on slit lamp

biomicroscopy findings as Gr.1a- non diffuse CSME, Gr.1b- diffuse

CSME, Gr.2-CSME with ERM, Gr.3- CSME with VMT/thickened

posterior hyaloid, Gr.4- CSME with CME. A diagnosis of diffuse CSME

was made if CSME involved the perifoveal region all around or atleast

three quadrants. FFA was done to classify the disease, to diagnose early

PDR, CME and to rule out macular ischemia. Macular ischemia was

defined on FFA as enlargement of foveal avascular zone compared to

other eye with area of segmental/focal perifoveal capillary loss. Patients

with macular ischemia were excluded from the study as these patients

could alter the interpretation of results, which also aimed at correlating

visual deficit with biomicroscopic and OCT features. OCT stratus-4 was

done in all eyes, preferably a line scan programme was chosen and the

image processed and analyzed. Based on OCT findings, we classified

CSME into five groups, Gr.1- macular thickening with only spongy

edema, Gr.2- macular thickening with ERM, Gr.3- macular thickening

with VMT, Gr.4- macular thickening with CME and Gr.5- macular

thickening with SRF.

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OBSERVATION Of the total 70 patients, there were 17 patients in 40-49yrs age

group (24%), 29 in 50-59 yrs age group (42%), 21 in 60-69 age group

(30%), 3 in 70-79 age group (4%) and none above 80 yrs. Males

predominated in the study with 66%. The male: female ratio was 2:1. Of

the 70 patients, 45 had NPDR (64%) and 25 had PDR (36%).

Biomicroscopically, 52% had diffuse CSME (Gr.Ia), 48% had focal

CSME (Gr.Ib), 16% had CSME with CME (Gr.IV) and 2% had CSME

associated with VMT (Gr.III) in the order of frequency. No patient had

ERM and SRF clinically.

OCT examination revealed macular thickening with spongy edema

in all patients (100%), macular thickening (ME) associated with CME in

38%, ME associated with VMT in 10%, ME associated with SRF in 8%

and ME associated with ERM in 2%. On OCT, eyes with spongy edema

showed diffuse thickening of macula with small cystic spaces. Eyes with

CME showed large cystic spaces in the foveolar and parafoveal region.

VMT was seen as hyper-reflective band in the vitreous, which was

adherent to the fovea, either centrally or paracentrally, causing traction

and pulling up the macula. None of the patients had a defect suggestive

of hole formation. SRF was seen as a subfoveal detachment on line

scans. ERM was identified as a hyper-reflective thickening at the level of

internal limiting membrane, causing distortion and flattening of the

foveal surface.

On comparing OCT with biomicroscopy/FFA, 38% of the eyes had

CME on OCT, compared to 16% detected on biomicroscopy/FFA. 8% of

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eyes had SRF with subfoveal detachment on OCT and was not identified

on biomicroscopy. 10% of eyes had VMT on OCT, compared to 2% on

biomicroscopy. 2% ERM was identified by OCT compared to none on

biomicroscopy.

Correlation with vision

Vision Biomicroscopy OCT

6/6 30% 30%

<6/6 70% 70%

Correlation of biomicroscopic and OCT finding with visual acuity

revealed that 30% of eyes had a visual acuity of 6/9 or better, while

70% had vision worse than 6/9. Of those in biomicroscopy group with

less vision, only 18% could be attributed to CME & VMT. No obvious

clinical cause for defective vision was detected in the rest 52% eyes with

visual loss. In OCT group, 58% could be attributed to CME, VMT, SRF &

ERM. No obvious clinical cause for defective vision was detected in the

rest 12% eyes with visual loss.

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STATISTICAL ANALYSIS

A comparative analysis between biomicroscopy and OCT evaluation was

done by Average method (Percentage calculation).

Shown below are the results obtained.

BIOMICROSCOPY OCT

SE 100 100

CME 16 38

ERM 0 2

VMT 2 10

SRF 0 8

Total number of samples = 100

Expected result in numbers = 100 (Assuming that both

BIOMICROSCOPY and OCT proves to be perfect.

Spongy edema BIOMICROSCOPY OCT

100 100 Result: By statistical analysis expected result and observer result

proved to be the same.

Inference: Both Biomicroscopy and OCT methods can be adopted.

Cystoid Macular Edema BIOMICROSCOPY OCT

16 38 Result: By Biomicroscopy, 16% of the total observations proved to be

valid and by OCT, 38%.

Inference: OCT is found to be more perfect compared to biomicroscopy.

OCT method can be adopted for CME.

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Epiretinal Membrane. BIOMICROSCOPY OCT

0 2 Result: By Biomicroscopy, 0% of the total observations proved to be

valid and by OCT, 2%.

Inference: OCT found comparatively better than biomicroscopy. OCT

method can be adopted for ERM.

VitreoMacular traction. BIOMICROSCOPY OCT

2 10 Result: By Biomicroscopy, 2% of the total observations proved to be

valid and by OCT, 10%.

Inference: OCT found comparatively better than biomicroscopy. OCT

method can be adopted for VMT.

Subretinal Fluid BIOMICROSCOPY OCT

0 8 Result: By Biomicroscopy, 0% of the total observations proved to be

valid and by OCT, 8%.

Inference: OCT is found to be more perfect compared to biomicroscopy.

OCT method can be adopted for SRF.

Conclusion: From the given set of samples detecting 5 items on these two tests,

except for SE, OCT is found to be statistically superior to

BIOMICROSCOPY based on average method. (Percentage calculation)

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ANALYSIS . Although slit lamp biomicroscopy is highly sensitive for qualitative

detection of CSME and FFA for detection of fluid leakage, various

studies have ascertained that qualitative assessment and quantitative

measurement of retinal thickening may correlate better with retinal

dysfunction in patients with CSME. OCT enables the clinician to study

their effects and show accurate subclinical retinal changes that may not

be even detectable in FFA.

Yang et al12 have suggested that the criteria of CSME seems to be

insufficient in identifying macular edema and that OCT may be more

sensitive than a clinical examination in assessing diabetic macular

edema and is a better tool for documenting changes in macular

thickening. OCT-identified spongy retinal thickness and / or CME was

seen in 58% of eyes without CSME in that series. In our series, we

found spongy thickening in all the eyes and CME in 38 % with macular

edema. Schaudig11 et al also found similar observations who in addition

also showed a significant increase in macular thickening in diabetic

patients without retinopathy compared to non-diabetic subjects.

Browning3 et al had demonstrated that the agreement between clinical

examination and OCT was good for moderate and severe macular

thickening (>300 microns) and poor for mild macular thickening (200-

300 microns). Most of these studies have also found a positive

correlation between increasing macular thickening and visual loss.

With the advent of newer medical therapies, intravitreal

triamcinalone, PST triamcinalone, intravitreal anti-VEGF therapy and

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vitrectomy for CSME, the role of laser in the management of CSME is

better reserved for selected groups of patients. OCT provides for a better

anatomical description of CSME for identification of the medically and

surgically treatable groups.

Hence our characterization of CSME patients based on OCT into

macular thickening with only spongy edema (Gr.-1), macular thickening

with ERM (Gr.-2), macular thickening with VMT (Gr.-3), macular

thickening with CME (Gr.-4) and macular thickening with SRF (Gr.-5) is

more relevant. Structural changes in OCT in our series correlate with

other data from literature. Otani et al found spongy retinal swelling in

88%, CME in 47% and SRF in 15% of eyes with CSME. Kim10 et al

found spongy retinal swelling in 97%, CME in 55%, SRF in 7%, VMT in

13% of eyes with CSME. Ozdek8 et al had reported spongy retinal

swelling in 66%, CME in 16% and SRF in 10% of eyes with diabetic

macular edema. In our study, we found spongy retinal swelling in100%,

CME in 38%, SRF in 8% and VMT in 10%.

On comparing OCT with biomicroscopy, 38% of the eyes had CME

on OCT, compared to 16% detected on biomicroscopy. 8% of eyes had

SRF with subfoveal detachment on OCT and was not identified on

biomicroscopy. 10% of eyes had VMT on OCT compared to 2% on

biomicroscopy. 2% of eyes had ERM identified by OCT compared to

none on biomicroscopy. Browning et3 al had also compared stereoscopic

slit lamp examination and OCT in the study of CSME and concluded

that stereoscopic slit lamp examination of the macula was less sensitive

than OCT for detection of diabetic macular edema. Strom6 et al had

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found an agreement of 89% on the exact location and 84% agreement

on the exact area of CSME when he compared biomicroscopy with OCT

and found the latter to be more superior.

In our study, 38% of the eyes had CME on OCT, compared to 16%

detected on biomicroscopy. Ozdek8 et al also found that 40% of CME

detected on OCT were not detected by biomicroscopy and 63% were not

detected even on fluorescein angiography. OCT is thus a better

diagnostic tool to diagnose CME in patients with diabetic retinopathy

than biomicroscopy or FFA. Kim et al also had reported that the

presence of CME in patients with CSME was significantly associated

with worse vision. In our study, 8% of the eyes had SRF with subfoveal

detachment, which could not be detected on biomicroscopy or FFA.

Most series have found SRF in 8-12% of eyes with CSME. Ozdemir14 et

al had reported that 31% of diabetic CMEs had subretinal fluid.

Previously it was believed that SRF was seen in eyes with taut thickened

posterior hyaloid, but many series had found evidence to the contrary.

Thomas et al7 found SRF to be associated with taut hyaloid in only 33%

of eyes and the rest without posterior hyaloid separation.

10% of eyes in our series had VMT on OCT compared to 2% on

biomicroscopy. VMT has been reported by various authors between 10-

60% of eyes with CSME. One study which specifically looked at

vitreoretinal interface changes in CSME found no PVD in 40% eyes, 53%

perifoveal PVD, 2% with incomplete PVD attached to disc and 6% with

complete PVD. These results show that though PVD is not the main

factor involved in the pathogenesis of diabetic macular edema,

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perifoveal PVD may have a role in the development of this complication.

This may have a bearing on planning management strategies especially

with regards to indications for vitrectomy for CSME.

ERM was also detected in 2% of eyes on OCT compared to none

on biomicroscopy in our study. Subtle ERM may therefore be missed on

routine clinical examination and may need OCT to diagnose it. Wilkins

et al2 found two types of ERM in patients with CSME, globally adherent

ERM in 67% and focally adherent ERM n 33%. This may be another

indication for vitrectomy in CSME.

As macular ischemia can be a cause of visual defects in patients

with CSME, the present study excluded this subgroup of patients

during the analysis. Correlation of biomicroscopic finding with visual

acuity revealed that 30% of eyes had a visual acuity of 6/9 or better,

while 70% had vision worse than 6/9. Of those with less vision, only

18% could be attributed to CME & VMT. No obvious clinical cause for

defective vision was detected in the rest 52% eyes with visual loss.

OCT evaluation of those eyes with visual acuity of less than 6/9

revealed CME in 38% of these eyes, VMT in 10% eyes, SRF in 8% eyes

and ERM in 2% of eyes, thereby offering a better understanding of the

cause of visual loss in these patients. Alkuraya et al had reported that

there was a positive correlation between the type of OCT finding and

visual acuity. Patients with CME and VMT had worse vision. Most of the

other series had reported that the visual acuity correlated better with

macular thickness, ie. more the central foveal thickness, worse the

vision. It is also known that the central foveal thickness increases with

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the different types of OCT presentations, being least for spongy

thickening, moderate for CME/SRF and highest for VMT and thus

visual loss mirrors these changes.

Thus these structural changes correlate better with the visual

defects the patients with CSME have in the absence of macular

ischemia in our series. Detection of these findings has a bearing in

planning treatment strategies. Eyes with CME and SRF will probably

respond poorly to conventional laser and require additional medical

management in the form of IVTA or PST. Eyes with VMT and ERM

probably are poor candidates for laser and are better managed by

primary vitrectomy. Identification of these findings on OCT will optimize

treatment in CSME, which will have a bearing on the final visual acuity

maintained or achieved.

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CONCLUSION

We found that OCT is a useful technique for quantitative

measurement and helps in better anatomical characterization of CSME

than biomicroscopy and thereby more relevant while planning

management strategies, followup, prognosis and predicting visual

income.

We found that OCT is better compared with biomicroscopy to

diagnose CME, to detect subretinal fluid with subfoveal detachment and

to study the vitreoretinal interface changes like vitreomacular traction &

epiretinal membrane.

OCT characterization of CSMEs identified groups that correlate

better with visual acuity than slit lamp biomicrocopy.

Patients with CSME and only spongy macular thickening on OCT

probably respond better to conventional laser therapy. Patients with

CME/SRF respond best to IVTA/PST with or without focal laser and

patients with ERM/VMT respond best with vitrectomy.

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ILLUSTRATIONS

==============================================================

=

Spongy edema on OCT only

CME on OCT only

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=====================================================

=

VMT on OCT only

SRF on OCT only

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Comparison – OCT Vs Biomicroscopy

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0 2 0

38

8 10

20 5 10 15 20 25 30 35 40

CME

SRF VMT ERM

%

BiomicroscopyOCT

ERM on OCT only

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REFERENCES 1. A standardized method for reporting changes in macular thickening

using optical coherence tomography; Chan A, Duker JS; Arch Ophthalmol, Jul2005, 123 (7)

2. Characterization of epiretinal membrane using optical coherence tomography, Wilkins JR et al; Ophthal 1996; 103(12): 2142-51

3. Comparison of the clinical diagnosis of diabetic macular edema with diagnosis by optical coherence tomography, Browning DJ et al; Ophthalmology 2004; 111(4): 712-5

4. Detection of diabetic foveal edema – contact lens biomicroscopy compared with optical coherence tomography, Brow JC et al; Arch Ophthal 2004; 122(3): 330-5

5. Diabetic macular edema – an OCT based classification; Panozzo G et al, Semin Ophthal, 2004; 19(1-2): 13-20

6. Diabetic macular edema assessed with optical coherence tomography and stereo fundus photography, Strom C et al; Invest Ophthal Visual Sciences 2002; 43(1): 241-45

7. Frequency and associations of a taut thickened hyaloid, partial vitromacular separation and subretinal fluid in patients with diabetic macular edema, Thomas D et al; Retina 2005; 25(7): 883-8

8. Optical Coherence Tomographic Assessment of Diabetic Macular Edema -Comparison with Fluorescein Angiographic and Clinical Findings; Sengui C Ozdek, Alper Erdinc, Gokhan Gurelik; Ophthalmologica 2005, 219(2): 86-92

9. Optical coherence tomography assessment of the vitreoretinal relationship in diabetic macular edema, Gaucher D et al; Am J Ophthal 2005; 139(5): 807-13`

10. Optical Coherence tomographic patterns of diabetic macular edema; Kim BY et al; Am J Ophthal, 2006; 142(3): 405-12

11. Optical coherence tomography for retinal thickness measurement in diabetic patients without clinically significant macular edema; Schaudig et al; Ophthal Surg Laser 2000; 31(3): 182-6

12. Quantitative Assessment of Retinal Thickness in Diabetics with or without CSME using OCT, Yang CS, Cheng CY; Acta Ophthalmol Scand 2001; 79(3): 266-70

13. Retinal Thickness Study with OCT in patients with Diabetes; Hortensia, Sanchaez-Tocino, Alvarez –Vidal; Investigative Ophthalmology & Visual Sciences 2002 May, 43

14. Serous macular detachment in diabetic cystoid macular edema, Ozdemir H et al; Acta Ophthal Scand 2005; 83(1): 63-6

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DECLARATION

I, Dr. ANU ANNA PAUL hereby declare that this dissertation

entitled “COMPARITIVE EVALUATION OF CLINICALLY SIGNIFICANT

MACULAR EDEMA WITH OCT & SLIT LAMP BIOMICROSCOPY.” is

an original work done by me at Chaithanya Eye Hospital & Research

Institute, Trivandrum

Dr. Anu Anna Paul MBBS, D.O, DNB, FMRD